Recombinant viral capsid protein VP1 suppresses lung cancer metastasis by inhibiting COX-2/PGE2 and MIG-7
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Ming-Yi Ho1, Shao-Wen Hung2, Chi-Ming Liang1,3, Shu-Mei Liang1,2
1 Genomics Research Center, Academia Sinica, Taipei, Taiwan, ROC
2 Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, ROC
3 Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, ROC
Chi-Ming Liang, email:
Shu-Mei Liang, email:
Keywords: Migration inducting gene-7 (MIG-7), Cyclooxygenase-2 (COX-2), Integrin-linked kinase (ILK), rVP1, Cancer metastasis, EMT
Received: March 24, 2014 Accepted: May 27, 2014 Published: May 29, 2014
Recombinant capsid protein VP1 (rVP1) of foot-and-mouth disease virus binds to integrins to modulate Akt/GSK3-β signaling and suppress migration/invasion and metastasis of cancer cells, but the underlying molecular mechanism is unclear. Here, we showed that the rVP1-mediated inhibition of Akt/GSK3-β signaling and cell migration/invasion was accompanied by downregulation in phosphatidylinositol (3,4,5)-triphosphate (PIP3), integrin-linked kinase (ILK) and IKK/NF-κB signaling as well as suppression of COX-2/PGE2 and MIG-7. Addition of PIP3 or overexpression of ILK reversed the rVP1-induced inhibition of IKK/NF-κB signaling, COX-2 and MIG-7. The rVP1-mediated downregulation of COX-2/PGE2 and MIG-7 led to not only attenuation of epithelial-mesenchymal transition, MMP2 activity and invasion of lung cancer cells in vitro but also decreased tumor growth and metastasis of lung cancer in xenograft mice. Moreover, downregulation of COX-2/PGE2 and MIG-7 significantly prolonged the overall and disease-free survival of lung cancer-bearing mice. These results suggest that rVP1 inhibits cancer invasion/metastasis, partly if not mainly, via downregulating integrin/PI3K/Akt, ILK and IKK/NF-κB signaling to suppress expression of COX-2/PGE2 and MIG-7.
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